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The topic of This Month Vol.39 No.3(No.457)

Rubella and congenital rubella syndrome in Japan as of January 2018

(IASR Vol. 39 p29-31: March, 2018)

Rubella is an acute infectious disease caused by rubella virus.  The three major clinical signs of rubella are rash, fever, and lymphadenopathy.  Although the symptoms of rubella are generally mild, serious complications, including encephalitis and thrombocytopenic purpura, can occur in rare cases.  Rubella virus infection in susceptible pregnant women can result in prenatal transmission to the fetus.  In particular, maternal infections that occur before a gestational age of 20 weeks can cause infants to be born with congenital rubella syndrome (CRS), which manifests as various signs/symptoms, including heart defects, cataracts, hearing loss, low birth weight, thrombocytopenic purpura, and psychomotor retardation (see p.33 of this issue).  Effective and safe vaccines are available for preventing rubella and CRS.

Together with the elimination of measles, the World Health Organization (WHO) and others are promoting various activities aimed at accelerating the elimination of rubella. The “Global Vaccine Action Plan 2011-2020”, which was endorsed by the 65th World Health Assembly in 2012, aims to eliminate measles and rubella in at least five WHO regions by 2020. The Japanese Ministry of Health, Labour and Welfare has issued “Guidelines for the Prevention of Specific Infections: Rubella” (Ministry of Health, Labour and Welfare notice No. 122, March 28, 2014), which describes measures that would help attain the goal of eliminating CRS occurrence in newborns as soon as possible, along with elimination of rubella by FY2020 in Japan. Furthermore, in December 2017 the guidelines were revised as follows: from January 1, 2018, 1) patients diagnosed with rubella should be immediately notified, 2) active epidemiological investigation should be conducted after occurrence of even a single case of rubella, and 3) as a rule, viral genome testing should be conducted for all suspected cases (see p.31 of this issue).

Notifications of rubella and CRS according to the National Epidemiological Surveillance of Infectious Diseases (NESID) system

Rubella is classified as a Category V infectious disease, requiring notification of all cases (http://www.niid.go.jp/niid/images/iasr/36/425/de4251.pdf). A nationwide rubella epidemic occurred in Japan between 2012 and 2013, and 2,386 and 14,344 cases were reported in 2012 and 2013, respectively (Fig. 1). After this epidemic, the number of cases decreased, with 319, 163, 126, and 91 cases in 2014, 2015, 2016, and 2017, respectively (Fig. 1).

As for the sex distribution of rubella, while males accounted for 77% of all cases in 2013, they accounted for 58-66% between 2014 and 2017 (Fig. 1). Adults comprised 90% of male cases and 78% of female cases in 2013 (Fig. 2). Many of the male cases were in their 20s-40s, while many female cases were in their 20s (Fig. 2). Approximately half of all female cases (16 cases) in 2017 were in their 20s-30s.

Between 2013 and 2017, 19-30% of all rubella cases had no history of vaccination with rubella-containing vaccine (1-7% of all cases were those aged <1 year and did not have the opportunity to receive the routine vaccine), 5-19% had received 1 dose, 1-9% had received 2 doses, and 48-65% had unknown vaccination history (Fig. 3).

CRS is also classified as a Category V infectious disease requiring notification of all cases, based on the Infectious Diseases Control Law (http://www.niid.go.jp/niid/images/iasr/36/425/de4252.pdf). Associated with the 2012-2013 epidemic, 45 CRS cases were notified between 2012 and 2014. A follow-up study found that, at the time of investigation, the case fatality of CRS cases was 24% (see p.33 of this issue). Since 2015, no further CRS cases have been reported as of February 1, 2018.

Current practice regarding laboratory diagnosis of rubella and CRS

Laboratory-confirmed cases of rubella accounted for 63-78% of all rubella cases that were reported under the NESID system between 2013 and 2017 (Fig. 4). Among laboratory-confirmed cases reported between April 1, 2014 and December 31, 2016, the most frequent method was detection of rubella-specific IgM (72%), followed by PCR-based detection of the rubella virus (23%) (some detected by both methods) (see p.34 of this issue). Throat swab, blood, and urine specimens are recommended for detection of the rubella virus genome. The detection rate of the rubella virus genome is high in the early stages after rash onset, and can be detected until about 7 days after rash onset (see p.35 of this issue). In contrast, as serum samples collected between 0 and 3 days after rash onset often do not have detectable rubella-specific IgM titers, it is recommended that tests be performed using serum samples collected ≥4 days after rash onset (ideally ≥5 days) to confirm the diagnosis (see p.37 of this issue). According to the revised guidelines, physicians are required to immediately notify a clinically diagnosed case of rubella; conduct tests for detecting serum antibodies, such as rubella-specific IgM; and send specimens to the public health institute (PHI) for conducting tests such as viral genome testing.

Laboratory testing is required for CRS notification. Between 2012 and 2014, 93% and 82% of CRS cases were identified via the detection of rubella-specific IgM and PCR-based detection of the rubella virus, respectively (some detected by both methods) (see p.33 of this issue). For diagnosing CRS based on the detection of specific IgM or the rubella virus genome, the sensitivity of detection is highest within the first 6 months after birth, and diagnosis becomes more difficult over time. Detecting the virus genome from a preserved umbilical cord is being considered as a possible laboratory method for diagnosing CRS for situations where a period of time has passed since birth (see p.38 of this issue).

Routine vaccination coverage of rubella-containing vaccines

Since FY2006, the routine immunization program in Japan has included the measles-rubella (MR) combination vaccine; children receive the first dose at 1 year of age (1st vaccination) and the second dose within 1 year prior to primary school entry (2nd vaccination). In FY2016, the vaccination coverage for the first and second doses of the vaccine were 97.2% and 93.1%, respectively. Thus, the target of 95% vaccination coverage was achieved for the first dose. To achieve the target for the second dose, further efforts are being made (http://www.niid.go.jp/niid/ja/diseases/ma/655-measles/idsc/7536-01-2016.html).

National epidemiological surveillance of vaccine-preventable diseases

In FY2017, the rubella hemagglutination-inhibiting antibody (HI) titers of serum samples collected from 5,656 healthy people (2,886 males and 2,770 females) from 18 prefectures were determined (Fig. 5). The antibody positivity rate (HI titer: ≥1:8) of males in their late 30s to early 50s was about 80%, which was considerably lower than that of their female counterparts. The seroprevalence of the HI antibody among males born between 1962 and 1978 (39-55 years of age at the time of the survey) remained unchanged at around 80% for 10 years between FY2008 and FY2017, and a large number of susceptible individuals still remain (see p.39 of this issue).

Efforts in the WHO Western Pacific Region (WPR)

In the WPR, the region which includes Japan, elimination of rubella has been set as a target goal. Rubella-containing vaccines have been introduced into routine immunization programs in most WPR countries or areas, and pediatric cases of rubella have declined markedly; however, outbreaks involving adults have been reported in some countries. In addition, a CRS surveillance system has yet to be established in some countries (see p.44 of this issue).

Future measures to be taken

To eliminate the occurrence of CRS as soon as possible and rubella by FY2020, measures such as the following should be taken. First, vaccination coverage rates of ≥95% should be achieved and maintained for each of the two routine rubella vaccination doses. Second, women of childbearing age, adult males (especially males who live with or have close contact with pregnant women), travelers to rubella-endemic countries, and medical personnel should be recommended to get vaccinated with a rubella-containing vaccine, and an environment that facilitates vaccination should be fostered. Third, there should be early detection of rubella patients along with interruption of disease transmission. Lastly, the nucleotide sequence of the rubella virus genome should be actively analyzed to clarify the transmission routes of the virus.

In the 2012-2013 epidemic, the majority of rubella patients were adult males, and transmission mainly occurred in the workplace. To prevent the resurgence of a similar epidemic, it is important to reduce the number of susceptible individuals among adult males. Furthermore, the implementation of control measures at workplaces and those pertaining to travel to endemic countries is necessary. In Tokyo, a project to support companies that take measures to prevent infectious diseases, including rubella, was launched in October 2015 (see p.41 of this issue). The project, “Rubella Zero”, defined February 4 as “Rubella Zero” Day and raises awareness and disseminates information about rubella prevention (see p.43 of this issue). For these rubella response activities, cooperation among companies, medical personnel, local public health centers, and PHIs is imperative.

Copyright 1998 National Institute of Infectious Diseases, Japan